EFFICIENT SYNTHESIS OF RIBONUCLEOTIDE REDUCTASE INHIBITORS 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE (3-AP) AND 3-AMINO-4-METHYLPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE (3-AMP) VIA PALLADIUM-MEDIATED CROSS-COUPLING REACTIONS

An efficient synthesis of potent ribonucleotide reductases inhibitors 3-amino-pyridine-2-carboxaldehyde thiosemicarbazone (3-AP) and 3-amino -4-methyl-pyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) is descr ibed. The synthesis of 3-AP and 3-AMP was achieved in 4 and 5 steps, w ith overall yields of 61% and 39%, respectively. The synthesis feature d a convergent approach utilizing a Stille coupling strategy to prepar e vinylpyridine derivatives. A more economic way to synthesize vinylpy ridine using Heck reaction was also discussed. (C) 1997 Elsevier Scien ce Ltd. All rights reserved.